Design, Synthesis and Various Bioactivity of Acylhydrazone-Containing Matrine Analogues

Abstract

Compounds with acylhydrazone fragments contain amide and imine groups that can act as electron donors and acceptors, so they are easier to bind to biological targets and thus generally exhibit significant biological activity. In this work, acylhydrazone fragments were introduced to the C-14 or C-11 position of matrine, a natural alkaloid, aiming to enhance their biological activities. The result of this bioassay showed that many synthesized compounds exhibited excellent anti-virus activity against the tobacco mosaic virus (TMV). Seventeen out of 25 14-acylhydrazone matrine derivatives and 17 out of 20 11-butanehydrazone matrine derivatives had a higher inhibitory activity against TMV than the commercial antiviral agent Ribavirin (the in vitro activity, in vivo inactivation, curative and protection activities at 500 µg/mL were 40.9, 36.5 ± 0.9, 38.0 ± 1.6 and 35.1 ± 2.2%, respectively), and four 11-butanehydrazone matrine derivatives even had similar to or higher activity than the most efficient antiviral agent Ningnanmycin (55.4, 57.8 ± 1.4, 55.3 ± 0.5 and 60.3 ± 1.2% at 500 µg/mL for the above four test modes). Among them, the N-benzyl-11-butanehydrazone of matrine formed with 4-bromoindole-3-carboxaldehyde exhibited the best anti-TMV activity (65.8, 71.8 ± 2.8, 66.8 ± 1.3 and 69.5 ± 3.1% at 500 µg/mL; 29, 33.5 ± 0.7, 24.1 ± 0.2 and 30.3 ± 0.6% at 100 µg/mL for the above four test modes), deserving further investigation as an antiviral agent. Other than these, the two series of acylhydrazone-containing matrine derivatives were evaluated for their insecticidal and fungicidal activities. Several compounds were found to have good insecticidal activities against diamondback moth (Plutella xylostella) and mosquito larvae (Culex pipiens pallens), showing broad biological activities.

Design, Synthesis, and Antifungal Activity of Some Novel Phenylthiazole Derivatives Containing an Acylhydrazone Moiety

“…The above results demonstrated that phenylthiazole is a promising antifungal skeleton for discovering new fungicides. Acylhydrazone compounds possess a wide range of biological activities, such as antifungal [19][20][21][22][23][24], antibacterial [25][26][27], insecticidal [28], antiviral [29,30], and antitumor activities [31,32], which have been widely concerned in the field of pesticides and pharmaceuticals. At present, some compounds containing an acylhydrazone structure have been developed as pesticides or pharmaceuticals, such as benquinox (fungicide) [19,25,29], metaflumizone (insecticide) [20,23,29], and nitrofurazone (antibacterial drug) [31].…”

The design, synthesis, and biological activity assay of malononitrile oxime ether compounds as effective fungicides

“…Acylhydrazones as reactive groups include both amide and imine structures and therefore can act as both hydrogen bond donors and acceptors. 12 Acylhydrazones have a strong coordination ability and a variety of coordination modes that allow flexibility in the orientation of the acylhydrazone structure in space, 13 so they can easily form stable hydrogen bonds or other interactions with biological targets, increasing the affinity for the receptor and thus affecting its biological activity. 14 The commercially available fungicide benquinox (Fig.…”